Catalytic dehydrogenation of piperazine



Patented June 28, 1949 UNITED STATES PATENT p CATALYTIC DEH'YDRO'GENATIONOF PIPERAZINE James Kenneth Dixon, Riverside. Conn.,.assignor to American CyanamidtCompany, :New .York, N. Y., a corporation. .of .Maine No Drawing. Application April-12,1946, Serial N: 661,876

(crew-250) Claims.

This invention relatestto catalytic dehydro genation in the vapor phase of piperazine and/or hydrates of piperazines. More particularly, it relates to the use, as catalysts therefor, of a metal such as palladium. As such, the. present inven-'.

tion constitutes a continuation-in-part of my copendin original application Serial No. 443,703, filed May 20, 1942, now Patent No. 2,400,398.

Pyrazine, as an intermediate for the manufacture of aminopyrazines, and ultimately sulfanil-l amidopyrazines, has become of increasing commercial importance, particularly in the field of chemotherapy. Unfortunately, while pyrazine itself is comparatively well=known, processes for its roduction which are suitable for development:

on a commercial scale have not been available. In the past, production has always been on a comparatively small scale, by inefiicient processes giving yields of about 3-6%.

By way of contrast, piperazine, differing from;

pyrazine only by the degree of hydrogenation, may be obtained by a number of different. procedures and is commercially available either in relatively pure form or as a hydrate such as the hexahydrate. Accordingly, on the basis ofavail-u ability alone, piperazine would appear to be a suitable raw materialto serve as a commercial source of pyrazine. It would appear theoretically possible to convert piperazine, C4H10N2; to pyrazine, C4H4N2, simply by removing the extra hydro-1:

gens.

The simplicity of this reaction; however, is more apparent than real. Actually the dehydrogenation is very difficult to carry out. Prior to this invention, no method was known of carrying out this reaction in an economically'feasible manner. The reaction is difiicult to initiate, a high temperature being necessary. Therefore, the problem is complicated in that dehydrogenation from piperazine to pyrazine will not be the only reaction to occur. Under the temperature conditions required, the ring structure will be expected to be cracked with concurrent formationof side reaction products and ammonia. Therefore, the

reaction is not only difiicult to initiate but whem In fact, because ofthe must.lbe one meeting: .ldefinite; requirements. As

, aiirst considerationthecatalyst. must be capable .of initiatingand.carrying out dehydrogenation.

-Becondly, the .catalystmust have the minimum possible tendencyto. promote crackin both, of

.the piperazine .and of the dehydrogenation .products.

..able. at .a feasible temperature.

desirable. catalystalso must meet .certain economical, requirements if it is to be used in a feasible commercialprocess. .The catalystshould .be one whichdsreadily available, has a. reason- .able life, is, not poisoned by any.materials necessarily .presentinthe reaction. vessel and. is operreactivated. This latter is particularly important in a commercial operation. Finally, the desired .1.catalyst should be one adapted to use in a con- The catalyst should preferably be capable of being readily tinuous process.

These requirements make the search for a suit- ...able catalyst much more exacting. Nevertheless, .if such .a catalyst can befound, the process of continuously, converting piperazine to pyrazine :remains a prospectively desirable commercial operation.

. It is, therefore, the objectof the present inventionto, find a suitable. continuous process for the .dehydrogenation of piperazine to pyrazine on a commercially-feasible basis, It is also an equally important object of the invention to find a catalyst, or groupof catalysts, suitable for use in that process.

In generaL-thedesired objects of the present invention are accomplishedby continuous, catalytic dehydrogenation of the piperazine to pyra- .zine in the vapor phase. In sodoing, use is made of a palladium metal catalyst, inthe use of which .the side reaction products obtained are particularly low.

.;In general, the process steps of the present invention maybe simply carried. out. Piperazine is vaporized andthe resultantvapors, preferably after preheating, are passed. over the selected 1 dehydrogenation catalyst. The rateof vapor flow and. correspondingly the oontacttime-with the catalyst. may be regulated by. the rate at which ;.piperazine is .fed to. the vaporizer .and/or by blending an inert vapor therewith. Introduction of. the inertvapors may bebeforeor during the preheating. After being passed over. the catalyst, the reacted vaporsare condensed. and thepyrazine collected therefrom, usually byfractionation. If so desired .unreactedpiperazinecan .be. readily recovered and'recycled.

.As compared with the prior art processes, yieldconverter.

3 ing 3-6% of pyrazine, in the present process yields of up to about 25% or more of pyrazine can be obtained in a single pass through the catalytic zone. Byfirecycling the unreacted piperazine this can be raised to 60% or better with substantially 100% total piperazine conversion.

Whileitis an advantage of the present invention that it is not limited to any particular apparatus or organization of apparatus, certain elements are found to be extremely useful in carrying out the process. For example, the piperazine should pass through the catalytic zone ata predetermined rate. Therefore some feed control .means should be provided to perform this regulation. It is also more or less necessary to control the amount of diluent gas or vapor and thereby control the time .of contact with the catalyst.

The piperazine or'its hydrate may be fed directly to the chamber in which it may be vaporized, usually by heating. The resulting vapors may then I be picked up by a stream of inert gas and carried into contact with the catalyst. Or, if so desired,

the'inert carrier gas and the piperazine maybe -mixed prior to being fed to the vaporizer. This latter procedure is quite simple where the piperazine is fed to the apparatus in the form of a solution in a solventthe vapors of which are suitable as diluents.

From the vaporizer, the gas and vapor mixture is passed to a catalytic chamber in which the actual dehydrogenation takes place. The catalyst is usually contained in a tubular converter, which is preferably but notnecessarilyyertically positioned, Passage of the vapors may be either up or down, preferably the latter, when the converter is other than horizontal. A tubular chamber is preferable in that it promotes a more uniform distribution and flow through a packed acted piperazine, water or other liquids which may be condensed. This fractionator may be a" part of the condensing system itself or the total condensate may be collected and fractionated in a subsequent operation. The latter operation is preferable where water is present during the reaction since pyrazine and water appear-to form a constant boiling mixture and it may be desirable to dry the total condensate before fracitionation. Drying may be readily carried out by using an absorbent such as pelleted sodium hydroxide, anhydrous sodium sulphate, calcium chloride or the like.

Pipera'zine itself, a piperazine hydrate such as the hexahydrate or even in some cases volatile salts of piperazine may be used as a starting material in the present process. Each has certain From the catalyst chamber reacted order to insure steady flow it is helpful to feed the material to the apparatus as a liquid. Since the hydrate melts much more readily than piperazine itself, it has an advantage in this respect. Further, it is more readily vaporized than piperazine. On the other hand, when a hydrated form is used as the raw material more Water is present in the condensate with the resultant difficulty in isolating the pyrazine product. Neither form appears to exhibit any particular advantage so far as the actual degree of dehydrogenation which can be finally achieved is concerned. Accordingly, in thepresent specification and the accompanying claims the term piperazine is used generically to include piperazine in a hydrated form. 7

As a general practice the dilution of vapors being subjected to catalytic action in order to regulate the time of contact between vapor and catalyst, or to depress undesirable side reactions, has become more or less well known. In the present case, any inert gas may be used, It was found that good results'could be obtained using nitrogen.

It was also'found feasible to regulate the feed of piperazine by diluting it. A satisfactory procedure was found to exist in making up a solution of piperazine in a volatile inert solvent and allowing the solvent vapors to replace all or a maior portion of the diluent gas. Piperazine forms an approximately 4% solution in benzene at room temperature. Using such a substantially saturated solution was found to produce good results. Benzene didnot interfere with the catalytic reaction and because of its slow molecular weight permits a good dilution by weight while maintaining a, high mol ratio of diluent to piperazine. Other volatile-solvents can be used if so desired, piperazine being soluble for example in such solvents as quinoline, toluene and xylene. Although a saturated benzene solution produces good results, if it is desired to increase the piperazine-solvent ratio it is quite simple to volatilize the solvent separately and blend the vapors before or during preheating. One precaution should be observed in that the benzene or other diluent used should be as nearly sulfur-free as possible. While the catalytic material may be used per se a and effective dehydrogenation obtained, this is not necessarily the best practice. The 100% catalysts are difficult to use effectively. Physically, they are not easy to prepare and handle.

use: Similarly, the use of a 100% catalyst makes In use, it is difficult to obtain'effective utilization of the potential catalytic capabilities of the Whole catalyst mass. This makes for inefficient areactivation operation more difiicult to carry out efiiciently. Further, unsupported catalysts ordinarily have poor resistance to high temperature and trouble is usually encountered through sintering during use and reactivation.

Because of these factors, it is preferable that the catalyst be supported on a suitable carrier. For this purpose a number of materials have been found suitable. These include such materials as alumina factivated alumina, silica, Celite and charcoal. The particular carrier chosen should be one which is normally surfaceactive but which will not have any appreciable pyrolytic effect on the dehydrogenation reaction which is to'be carried out. Alumina clays with appreciable alkali or alkaline earth metal contents therefore are not productive of good supports.

advantages and disadvantages. For example, Use of. the catalystssof the present invention is a highly suitable carrier.

present invention is relatively simple.

characterized by the fact that effective results between about 250-350 0., this is somewhat lower than that consistently used in conjuction with dehydrogenation catalysts of the diflicultlyreducible oxide types and. with metals of the easily-reducible oxides. As a result, charcoal is It has the advantage that it may be readily burned out to permit recovery and redeposition of the expensive catalytic metals. On the other hand, because it is easily burned off a charcoal support is not wholly suited to reactivation since the temperatures required therefor are somewhat higher and tend to destroy th char-coal support. Activated alumina is readily available in several forms, is

mechanically strong, easily handled and is highly successful in use. It does not interfere with the action of the catalytic metal and is free from.

form .of broken granules screened to a suitable size. However, a preferred embodiment ofthe practice is to use preformed pellets of powdered material. The preformed pellets have a number of advantages. The size is chosen in accordance with the desired contact time. They are wholly uniform in size which permits of more ready and uniform packing of the converter column. The flow of vapors therethrough is therefore more uniform, the contact time is more easily estimated and held to the desired conditions.

Preparation of the catalysts for use in the An aqueous solution of a palladium salt, usually the chloride, is uniformly deposited on the carrier. While any salt may be used, the nitrate is usually readily available and being easily broken down is perhaps preferred. Preferably this deposition is carried out in two or three successive steps, approximately equal amounts being deposited in each step and the carrier being thoroughly dried 'between depositions. After deposition of the salt the composition is heated to break down the salt and then heated sufliciently to reduce the residue to the desired metal oxide. This usually may be done by heating up to less than about 400 C. but since the catalyst is frequently used at somewhat above this temperature it preferably should be calcined to a somewhat higher temperature. Finally, but not always necessarily, it is usually desirable that the calcined catalyst be given a treatment at about the expected reaction temperature range in an atmosphere of hydrogen.

Reaction temperatures used in the present process fall within the general range of about 250-450 C. The optimum results, however, are usually obtained at an intermediate value within this range. For the palladium metal catalysts of the present invention the most desirable range will be between 350-400" C. While this is considered the reaction temperature it is the temperature of the catalyst body. The actual temperature .of the vapors passing thereover may not exactly coincide since such temperatures are not only difficult to measure but vary with the feed rate and hence for any given catalyst volume on the time of contact. While the preferred range is usually between 350-400 0., such accurate control of the temperature is extremely diflicult to maintain over extended periods and the wider or even .450"C., is a good Contacttime, one of the most important controls, is easily regulated by the amount of matedefinitely preferable.

rial vaporized. As wasnoted above, it is preferredto pass fully vaporized material .over the catalyst. The rate of piperazine fed to the vaporizer therefore is a function of the contact time. Since piperazine is easily melted, it is easily fedper se as a fluid in amounts regulated by a displacement feeder, a simple flow meter or the like. On the other hand, as noted above, it may also be done as a solutionin a solvent. The inert solvent also serves as a diluent gas during reaction since it is fully vaporized. along with the solvent. As also noted: above, all or a part of the diluent, whether an inertor neutral gas or separately vaporized solvent may be blended with the vaporized piperazine.

In the present process use of some diluent is The amount of diluent used will vary, not only with the molecular weight some element of compromise.

of the chosen diluent, but also with a number of other factors.

the present reaction, as the partial pressure of piperazine is increased, the total piperazine throughput for a given apparatus and catalyst mass increases. But, the conversion to and yield of ammonia alsoincreases and the total conversion of piperazine, as well as the conversion to and yield of pyrazine falls off markedly. A good compromise of these factors, therefore, indicates that the partial pressure of pyrazine entering the conversion chamber should be from about 0.1 to

0.3 or 0.4 atmosphere.

Igrom the point of view of commercial practice the life of a catalyst and its susceptibility toreactivation are also important. In carrying out the development work on the catalysts of the present invention it was found that they could i be readily reactivated. That is, carbonaceous material deposited during the dehydrogenation process eventually. reduces the activity of the catalyst. These tarry materials may be removed by passing air or oxygen-containing gas over the catalyst. This reactivation is followed by reduction where necessary. The temperature during reactivation must be limited so that the exothermic reactivation process does not result in permanent sintering of the surface. It was also found advisable to keep the catalysts in an atmosphere of hydrogen wherever possible from the time it was reactivated to the time it was ready to be used again.

The invention will be more fully described in conjunction with the following example which is intended as illustrative only and not by way of limitation. Unless otherwise noted, all parts are by weight and percentages of conversion and yields are expressed in mol percent.

Example 18-25% of .pyrazine .were obtainedwinwa single;

pass at from about."350,-.450' .C. .withsunconverted :piperazine recovery of about 50-70%. The active life of the catalystdecreased-somewhat as thetemperatures went-above about 400 C.

The products were characterizedv by extremely low ammonia contents in thereacted vapors.

I claim:

1. The method of producing'pyrazine --which :comprises completely vaporizing .piperazine;

:passing the vaporized material-.over'a palladium dehydrogenation :catalyst -at dehydrogenation temperatures; condensing thec-ondensable: portion of the reacted vapors-and isolating the pyrazine content of thencondensate.

2. The method of producing ,pyrazine :which 20 comprises vcompletely vaporizing piperazine; passing: the vaporized material over a1 palladium dehydrogenation catalyst at'250450 C.; condensing the condensable portionof-the reacted vapors and isolating the pyraziner'content of the condensate.

3. A method according-toclaimpl intwhich the catalytic mass comprises about 2-20% 01. palladium on a surface-active,.n on-pyrolytic carmen 4. -A method according toclaim 1: in which the catalytic mass comprises about .'2+20%..of palladium on a charcoal carrier.

5. 'A method according: to claimzlwin which the catalytic mass comprises about.v 2-20% of palladium on an activated'alumina carrier.

6. A method according to claim 1 in-which the catalytic mass comprises about=2-20% I of palladium on-a charcoal carrier, the temperature being maintained .at1250-3507C.

.7. A method according ato; claimyl tin which the catalytic mass compriseszabouti:2 -20% =-.of palladium on an .activated clalumina; ;carrier, the temperature being maintained;at-s300+450:;0.

8;The method of producingapyrazine:wwhich comprises forming a mixture. of .;completely=va- 5 egenation temperatures; condensing thecondenwsa'ble; portion. of-Vthe reactedvapors and isolating the ,pyrazine content; of :thecondensate.

' 9. A .methodaccording. to claim 8 in which the di1-uent-.-is a completely vaporized 1 fluid selected 10 from 1 the groups consisting of water, benzene ggQUiIlOliiI-JG, xylene .land toluene.

1 4 10. 2A" methodj-zaccording 1 totclaim .8 in which the reactiomtemperature is z from about 250- -450 C.

11.-.-A method/according? toclaim :18 in which Lethe :catalytictmass acom-prisesabout 220% of palladium eon a surface-active, non-pyrolytic ccarrier.

12.. A..method accordingrto claim 8 in which .the .catalytictmass comprises about: 2-20% of .palladium on a charcoal. carrier.

..13. A .method accordingto claim 8 in which the catalytic mass comprises about.2-20% of utpalla-diumhon an activated. alumina carrier. 5 14. A. method according-to claim 8iin-which thecatalyticemass-.comprises about 2-20% of ,palladium .on-. a surface-active, non-pyrolytic carrier, the temperature being maintained .at .,.250-..350. C.

0 L15. .Almethod according to claim 8 in which the icatalytic mass. comprises,- about 2-20%. of

.,.palladium ion an l,activated..alumina carrier,

the temperature beingcmaintained at 300-45090.

W'JAM-ES .KENNETH DIXON.

REFERENCES CITED .Theefollolwing referenlcesaare: of. vrecordzin r: the (file ofrthis patent:

UNITED STATES PATENTS .aNam'e Date Groll .Dec. 19, 1939 Hull Feb. 10, 1942 Number 

